The light sensing and signaling processes of the human retina require a high level of support in terms of energy supply and waste removal to ensure optimal functionality. A monolayer of epithelial cells, known as the retinal pigmented epithelium (RPE) separates the light sensing and signaling processes from the blood supply of the choroid and it controls many bi-directional support functions. The RPE cells are attached to a basement membrane, known as Bruch's membrane, which is a thin extra-cellular matrix of collagen layers which act as a semi-permeable barrier between the RPE cells and blood vessels of the choroid. The work of Marshall, Hussain, Guo and Ahir, [Expression of Matalloproteinases from human retinal pigment epithelial cells and their effects on the hydraulic conductivity of Bruch's Membrane, Invest Ophthalmol Vis Sci. 2002 February;43(2):458-65] has shown that degradation of the transport functions of Bruch's membrane is a major contributor to loss or decline in visual function with normal aging or a more rapid decline due to diseases such as age-related macular degeneration (AMD). Although these transport functions begin to degrade from birth, serious vision loss may not occur until later in life when the RPE/Bruch's membrane/choroid complex degrades to a point at which it can no longer sustain the neuro-retina, resulting in atrophy of the neuro-retina or stress induced responses such as choroidal new vessel (CNV) growth.
Although changes in diet and environment have been recommended to reduce the rate of age related loss of visual acuity, no direct treatment for the retina exists, and almost all current treatments for AMD are focused on treating late stage complications such as CNV's. Current treatments for CNV's include photo-dynamic therapy (PDT) (as described in U.S. Pat. No. 5,756,541 assigned to QLT Phototherapeutics Inc) where a photosensitive drug is administered intravenously and then activated by a light source which is directed at the CNV, and intra-vitreal injections of drugs which inhibit the growth factors which promote new blood vessel growth (anti-VEGF).
Lasers have been used for many years to treat retinal disorders, predominately using their ability to coagulate tissue. The degree of laser energy absorption in retinal layers and structures is highly dependant on the wavelength used and one of the major absorbing chromophores within the retina is the melanin which pigments the RPE cells. Although the current retinal lasers use wavelengths that are strongly absorbed by the melanin of the RPE cells, the duration of the laser pulses which are currently used allows time for thermal diffusion from the RPE cells to adjacent structures and is particularly damaging to the neuro-retina resulting in permanent loss of visual function at the treatment site. Roider, Norman, Michaud, Thomas, Flotte and Birngruber [Response of the Retinal Pigment Epithelium to Selective Photocoagulation Arch Ophthalmology Vol 110, December 1992] describe that short duration laser pulses can be used to contain the energy within the RPE cells and prevent neuro-retinal damage, using a technique known as selective retinal therapy (SRT). SRT has been applied to a number of late stage retinal diseases with the aim of producing a therapeutic benefit by initiating a wound healing response at the level of the RPE, but with limited success, and the reason why a beneficial effect can be obtained in this way has not been explained.
The SRT method is well described in United Stated patent application 20040039378 by Lin in which a laser scanning device is used to provide very short irradiance times. While this patent describes the requirement for nanosecond duration exposures it is difficult to achieve the required radiant exposure level using the scanning method described.